Putrescine (or 1,4-butanediamine) is a type of polyamine, such as spermidine and spermine, and is found in gram-negative bacteria and fungi. Since putrescine is present in a wide range of concentrations in various species, it is expected to play an important role in the metabolism of microorganisms. Putrescine is produced mainly by chemical synthesis through acrylonitrile and succinonitrile from propylene. The chemical synthesis uses the substances derived from petrochemicals as starting materials and uses toxic chemicals, and thus it is not environmental-friendly and has a problem of oil depletion.
In order to resolve these problems, there has been much research on developing a method for biosynthesis of putrescine by using microorganisms that is more environmentally-friendly and reduces energy consumption. According to current knowledge, putrescine can be biosynthesized through two pathways from microorganisms. In one pathway, ornithine is produced from glutamate and the ornithine is decarboxylated to synthesize putrescine. In the other pathway, arginine is synthesized from the ornithine, agmatine is produced from arginine, and then putrescine is synthesized from the agmatine. In addition, there are other methods for synthesizing putrescine where the known enzymes involved in the synthetic pathways of putrescine are transformed in a target microorganism. For example, WO09/125,924 discloses a method for producing putrescine at high yield by inactivating the pathway involved in the decomposition and utilization of putrescine present in E. coli, by inactivating the pathway in which ornithine, a precursor of putrescine, is converted to arginine, and by enhancing the biosynthetic pathway of ornithine. An article published in 2009 discloses a method for producing putrescine in high concentration by introducing the protein that converts ornithine to putrescine into Corynebacterium strains which are not capable of producing putrescine and by enhancing the activity thereof (Qian et al., Biotechnol Bioeng, 104:4, 651-662, 2009).
The produced putrescine can be decomposed by microorganisms or used in other metabolism. For example, spermidine synthase (EC: 2.5.1.16, speE) which is expressed in E. coli and Corynebacterium glutamicum synthesizes spermidine from putrescine, and acetyltransferase (N-acetyltransferase) which is expressed in Candida boidinii acetylates putrescine to N-acetylputrescine. It is known that putrescine can be produced in high concentration in the E. coli strain that is modified to have weakened activity of spermidine acetyltransferase (EC: 2.3.1.57. speG) which exhibits high homology with the above acetyltransferase (Korean Patent No. 1188432).
Although the enzyme that acetylates putrescine to N-acetyl putrescine in the microorganism of Corynebacterium genus has not been identified yet, it is known that when the gene known to encode NCgl1469, which is a histone acetyltransferase HPA2 and related acetyltransferase, are deleted, the N-acetylation of cadaverine, a type of diamine, is specifically reduced (Kind et al., Appl Environ Microbiol, 76:15, 5175-5180, 2010). However, it was reported that the NCgl1469 does not use putrescine and 1,3-diaminopropane as a substrate. In other words, the NCgl1469 was presumed to have a specific activity only on cadaverine from among all different diamines. On the other hand, it is known that NCgl1469 exhibits the activity of acetyl glutamate synthase and ornithine acetyltransferase in Corynebacterium glutamicum to produce ornithine and arginine in high concentration, and when NCgl1469 is overexpressed in the Corynebacterium glutamicum, ornithine and arginine can be produced at high yield (Korea Patent No. 1174267). Likewise, the activity of NCgl1469 is specific to glutamate and cadaverine and the effect of NCgl1469 in increasing the productivity of ornithine are known, but it has not been identified yet whether NCgl1469 is associated with the production of putrescine.